From MIT: “Chemists boost boron’s utility”

MIT News


From MIT News

March 2, 2021
Anne Trafton

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MIT chemists have created a new boron-containing chemical group that is 10,000 times more stable than boron on its own.
Credits: MIT News.

Boron, a metalloid element that sits next to carbon in the periodic table, has many traits that make it potentially useful as a drug component. Nonetheless, only five FDA-approved drugs contain boron largely because molecules that contain boron are unstable in the presence of molecular oxygen.

MIT chemists have now designed a boron-containing chemical group that is 10,000 times more stable than its predecessors. This could make it possible to incorporate boron into drugs and potentially improve the drugs’ ability to bind their targets, the researchers say.

“It’s an entity that medicinal chemists can add to compounds they’re interested in, to provide desirable attributes that no other molecule will have,” says Ron Raines, the Firmenich Professor of Chemistry at MIT and the senior author of the new study.

To demonstrate the potential of this approach, Raines and his colleagues showed that they could improve the protein-binding strength of a drug that is used to treat diseases caused by the misfolding of a protein called transthyretin.

MIT graduate student Brian Graham and former graduate student Ian Windsor are the lead author of the study, which appears this week in the PNAS. Former MIT postdoc Brian Gold is also an author of the paper.

Hungry for electrons

Boron is most commonly found in the Earth’s crust in the form of minerals such as borax. It contains one fewer electron than carbon and is hungry for additional electrons. When boron is incorporated into a potential drug compound, that hunger for electrons often leads it to interact with an oxygen molecule (O2) or another reactive form of oxygen, which can destroy the compound.

The boron-containing drug bortezomib, which prevents cells from being able to break down used proteins, is an effective cancer chemotherapy agent. However, the drug is unstable and is destroyed readily by oxygen.

Previous research has shown that the stability of boron-containing compounds can be increased by appending benzene- a six-carbon ring. In 2018, Raines and his colleagues used this approach to create a modified version of a drug called darunavir, a protease inhibitor used to treat HIV/AIDS. They found that this molecule bound to HIV protease much more tightly than the original version of darunavir. However, later studies revealed that the molecule still did not survive for long under physiological conditions.

In the new paper, the researchers decided to use a chemical group called a carboxylate to further anchor boron within a molecule. An oxygen atom in the carboxylate forms a strong covalent bond — a type of bond that involves sharing pairs of electrons between atoms — with boron.

“That covalent bond pacifies the boron,” Raines says. “The boron can no longer react with an oxygen molecule in the way that boron in other contexts can, and it still retains its desirable properties.”

One of those desirable properties is the ability to form reversible covalent bonds with the target of the drug. This reversibility could prevent drugs from permanently locking onto incorrect targets, Raines says. Another useful feature is that the boron-containing group — also known as benzoxaboralone — forms many weaker bonds called hydrogen bonds with other molecules, which helps to ensure a tight fit once the right target is located.

Greater stability

Once they showed that benzoxaboralone was significantly more stable than boron in other contexts, the researchers used it to create a molecule that can bind to transthyretin. This protein, which carries hormones through the bloodstream, can cause amyloid diseases when it misfolds and clumps. Drugs that bind to transthyretin can stabilize it and prevent it from clumping. The research team showed that adding benzoxaboralone to an existing drug helped it to bind strongly with transthyretin.

Benzoxaboralone may offer medicinal chemists a useful tool that they can explore in many different types of drugs that bind to proteins or sugar molecules, Raines says. His lab is now working on a new version of darunavir that incorporates benzoxaboralone. They recently developed a way to synthesize this compound and are now in the process of measuring how strongly it binds to HIV protease.

“We are working hard on this because we think that this scaffold will provide much greater stability and utility than any other presentation of boron in a biological context,” Raines says.

MIT has filed for a patent on the use of benzoxaboralone in medicinal chemistry and other areas. The research was funded by the National Institutes of Health and the National Science Foundation.

See the full article here .


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Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. The institute has an urban campus that extends more than a mile (1.6 km) alongside the Charles River. The institute also encompasses a number of major off-campus facilities such as the MIT Lincoln Laboratory, the Bates Center, and the Haystack Observatory, as well as affiliated laboratories such as the Broad and Whitehead Institutes.

MIT Haystack Observatory, Westford, Massachusetts, USA, Altitude 131 m (430 ft).

Founded in 1861 in response to the increasing industrialization of the United States, MIT adopted a European polytechnic university model and stressed laboratory instruction in applied science and engineering. It has since played a key role in the development of many aspects of modern science, engineering, mathematics, and technology, and is widely known for its innovation and academic strength. It is frequently regarded as one of the most prestigious universities in the world.

As of December 2020, 97 Nobel laureates, 26 Turing Award winners, and 8 Fields Medalists have been affiliated with MIT as alumni, faculty members, or researchers. In addition, 58 National Medal of Science recipients, 29 National Medals of Technology and Innovation recipients, 50 MacArthur Fellows, 80 Marshall Scholars, 3 Mitchell Scholars, 22 Schwarzman Scholars, 41 astronauts, and 16 Chief Scientists of the U.S. Air Force have been affiliated with MIT. The university also has a strong entrepreneurial culture and MIT alumni have founded or co-founded many notable companies. MIT is a member of the Association of American Universities (AAU).

Foundation and vision

In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a “Conservatory of Art and Science”, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, proposed by William Barton Rogers, was signed by John Albion Andrew, the governor of Massachusetts, on April 10, 1861.

Rogers, a professor from the University of Virginia, wanted to establish an institution to address rapid scientific and technological advances. He did not wish to found a professional school, but a combination with elements of both professional and liberal education, proposing that:

The true and only practicable object of a polytechnic school is, as I conceive, the teaching, not of the minute details and manipulations of the arts, which can be done only in the workshop, but the inculcation of those scientific principles which form the basis and explanation of them, and along with this, a full and methodical review of all their leading processes and operations in connection with physical laws.

The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars and laboratories.

Early developments

Two days after MIT was chartered, the first battle of the Civil War broke out. After a long delay through the war years, MIT’s first classes were held in the Mercantile Building in Boston in 1865. The new institute was founded as part of the Morrill Land-Grant Colleges Act to fund institutions “to promote the liberal and practical education of the industrial classes” and was a land-grant school. In 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst. In 1866, the proceeds from land sales went toward new buildings in the Back Bay.

MIT was informally called “Boston Tech”. The institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, and the size of the student body increased to more than one thousand.

The curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership. During these “Boston Tech” years, MIT faculty and alumni rebuffed Harvard University president (and former MIT faculty) Charles W. Eliot’s repeated attempts to merge MIT with Harvard College’s Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard. In its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually, the MIT Corporation approved a formal agreement to merge with Harvard, over the vehement objections of MIT faculty, students, and alumni. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme.

In 1916, the MIT administration and the MIT charter crossed the Charles River on the ceremonial barge Bucentaur built for the occasion, to signify MIT’s move to a spacious new campus largely consisting of filled land on a one-mile-long (1.6 km) tract along the Cambridge side of the Charles River. The neoclassical “New Technology” campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious “Mr. Smith”, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of film production and processing, and founded Eastman Kodak. Between 1912 and 1920, Eastman donated $20 million ($236.6 million in 2015 dollars) in cash and Kodak stock to MIT.
Curricular reforms

In the 1930s, President Karl Taylor Compton and Vice-President (effectively Provost) Vannevar Bush emphasized the importance of pure sciences like physics and chemistry and reduced the vocational practice required in shops and drafting studios. The Compton reforms “renewed confidence in the ability of the Institute to develop leadership in science as well as in engineering”. Unlike Ivy League schools, MIT catered more to middle-class families, and depended more on tuition than on endowments or grants for its funding. The school was elected to the Association of American Universities in 1934.

Still, as late as 1949, the Lewis Committee lamented in its report on the state of education at MIT that “the Institute is widely conceived as basically a vocational school”, a “partly unjustified” perception the committee sought to change. The report comprehensively reviewed the undergraduate curriculum, recommended offering a broader education, and warned against letting engineering and government-sponsored research detract from the sciences and humanities. The School of Humanities, Arts, and Social Sciences and the MIT Sloan School of Management were formed in 1950 to compete with the powerful Schools of Science and Engineering. Previously marginalized faculties in the areas of economics, management, political science, and linguistics emerged into cohesive and assertive departments by attracting respected professors and launching competitive graduate programs. The School of Humanities, Arts, and Social Sciences continued to develop under the successive terms of the more humanistically oriented presidents Howard W. Johnson and Jerome Wiesner between 1966 and 1980.

MIT’s involvement in military science surged during World War II. In 1941, Vannevar Bush was appointed head of the federal Office of Scientific Research and Development and directed funding to only a select group of universities, including MIT. Engineers and scientists from across the country gathered at MIT’s Radiation Laboratory, established in 1940 to assist the British military in developing microwave radar. The work done there significantly affected both the war and subsequent research in the area. Other defense projects included gyroscope-based and other complex control systems for gunsight, bombsight, and inertial navigation under Charles Stark Draper’s Instrumentation Laboratory; the development of a digital computer for flight simulations under Project Whirlwind; and high-speed and high-altitude photography under Harold Edgerton. By the end of the war, MIT became the nation’s largest wartime R&D contractor (attracting some criticism of Bush), employing nearly 4000 in the Radiation Laboratory alone and receiving in excess of $100 million ($1.2 billion in 2015 dollars) before 1946. Work on defense projects continued even after then. Post-war government-sponsored research at MIT included SAGE and guidance systems for ballistic missiles and Project Apollo.

These activities affected MIT profoundly. A 1949 report noted the lack of “any great slackening in the pace of life at the Institute” to match the return to peacetime, remembering the “academic tranquility of the prewar years”, though acknowledging the significant contributions of military research to the increased emphasis on graduate education and rapid growth of personnel and facilities. The faculty doubled and the graduate student body quintupled during the terms of Karl Taylor Compton, president of MIT between 1930 and 1948; James Rhyne Killian, president from 1948 to 1957; and Julius Adams Stratton, chancellor from 1952 to 1957, whose institution-building strategies shaped the expanding university. By the 1950s, MIT no longer simply benefited the industries with which it had worked for three decades, and it had developed closer working relationships with new patrons, philanthropic foundations and the federal government.

In late 1960s and early 1970s, student and faculty activists protested against the Vietnam War and MIT’s defense research. In this period MIT’s various departments were researching helicopters, smart bombs and counterinsurgency techniques for the war in Vietnam as well as guidance systems for nuclear missiles. The Union of Concerned Scientists was founded on March 4, 1969 during a meeting of faculty members and students seeking to shift the emphasis on military research toward environmental and social problems. MIT ultimately divested itself from the Instrumentation Laboratory and moved all classified research off-campus to the MIT Lincoln Laboratory facility in 1973 in response to the protests. The student body, faculty, and administration remained comparatively unpolarized during what was a tumultuous time for many other universities. Johnson was seen to be highly successful in leading his institution to “greater strength and unity” after these times of turmoil. However six MIT students were sentenced to prison terms at this time and some former student leaders, such as Michael Albert and George Katsiaficas, are still indignant about MIT’s role in military research and its suppression of these protests. (Richard Leacock’s film, November Actions, records some of these tumultuous events.)

In the 1980s, there was more controversy at MIT over its involvement in SDI (space weaponry) and CBW (chemical and biological warfare) research. More recently, MIT’s research for the military has included work on robots, drones and ‘battle suits’.

Recent history

MIT has kept pace with and helped to advance the digital age. In addition to developing the predecessors to modern computing and networking technologies, students, staff, and faculty members at Project MAC, the Artificial Intelligence Laboratory, and the Tech Model Railroad Club wrote some of the earliest interactive computer video games like Spacewar! and created much of modern hacker slang and culture. Several major computer-related organizations have originated at MIT since the 1980s: Richard Stallman’s GNU Project and the subsequent Free Software Foundation were founded in the mid-1980s at the AI Lab; the MIT Media Lab was founded in 1985 by Nicholas Negroponte and Jerome Wiesner to promote research into novel uses of computer technology; the World Wide Web Consortium standards organization was founded at the Laboratory for Computer Science in 1994 by Tim Berners-Lee; the OpenCourseWare project has made course materials for over 2,000 MIT classes available online free of charge since 2002; and the One Laptop per Child initiative to expand computer education and connectivity to children worldwide was launched in 2005.

MIT was named a sea-grant college in 1976 to support its programs in oceanography and marine sciences and was named a space-grant college in 1989 to support its aeronautics and astronautics programs. Despite diminishing government financial support over the past quarter century, MIT launched several successful development campaigns to significantly expand the campus: new dormitories and athletics buildings on west campus; the Tang Center for Management Education; several buildings in the northeast corner of campus supporting research into biology, brain and cognitive sciences, genomics, biotechnology, and cancer research; and a number of new “backlot” buildings on Vassar Street including the Stata Center. Construction on campus in the 2000s included expansions of the Media Lab, the Sloan School’s eastern campus, and graduate residences in the northwest. In 2006, President Hockfield launched the MIT Energy Research Council to investigate the interdisciplinary challenges posed by increasing global energy consumption.

In 2001, inspired by the open source and open access movements, MIT launched OpenCourseWare to make the lecture notes, problem sets, syllabi, exams, and lectures from the great majority of its courses available online for no charge, though without any formal accreditation for coursework completed. While the cost of supporting and hosting the project is high, OCW expanded in 2005 to include other universities as a part of the OpenCourseWare Consortium, which currently includes more than 250 academic institutions with content available in at least six languages. In 2011, MIT announced it would offer formal certification (but not credits or degrees) to online participants completing coursework in its “MITx” program, for a modest fee. The “edX” online platform supporting MITx was initially developed in partnership with Harvard and its analogous “Harvardx” initiative. The courseware platform is open source, and other universities have already joined and added their own course content. In March 2009 the MIT faculty adopted an open-access policy to make its scholarship publicly accessible online.

MIT has its own police force. Three days after the Boston Marathon bombing of April 2013, MIT Police patrol officer Sean Collier was fatally shot by the suspects Dzhokhar and Tamerlan Tsarnaev, setting off a violent manhunt that shut down the campus and much of the Boston metropolitan area for a day. One week later, Collier’s memorial service was attended by more than 10,000 people, in a ceremony hosted by the MIT community with thousands of police officers from the New England region and Canada. On November 25, 2013, MIT announced the creation of the Collier Medal, to be awarded annually to “an individual or group that embodies the character and qualities that Officer Collier exhibited as a member of the MIT community and in all aspects of his life”. The announcement further stated that “Future recipients of the award will include those whose contributions exceed the boundaries of their profession, those who have contributed to building bridges across the community, and those who consistently and selflessly perform acts of kindness”.

In September 2017, the school announced the creation of an artificial intelligence research lab called the MIT-IBM Watson AI Lab. IBM will spend $240 million over the next decade, and the lab will be staffed by MIT and IBM scientists. In October 2018 MIT announced that it would open a new Schwarzman College of Computing dedicated to the study of artificial intelligence, named after lead donor and The Blackstone Group CEO Stephen Schwarzman. The focus of the new college is to study not just AI, but interdisciplinary AI education, and how AI can be used in fields as diverse as history and biology. The cost of buildings and new faculty for the new college is expected to be $1 billion upon completion.

The Laser Interferometer Gravitational-Wave Observatory (LIGO) was designed and constructed by a team of scientists from California Institute of Technology, MIT, and industrial contractors, and funded by the National Science Foundation.

MIT/Caltech Advanced aLigo .

It was designed to open the field of gravitational-wave astronomy through the detection of gravitational waves predicted by general relativity. Gravitational waves were detected for the first time by the LIGO detector in 2015. For contributions to the LIGO detector and the observation of gravitational waves, two Caltech physicists, Kip Thorne and Barry Barish, and MIT physicist Rainer Weiss won the Nobel Prize in physics in 2017. Weiss, who is also an MIT graduate, designed the laser interferometric technique, which served as the essential blueprint for the LIGO.

The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

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